Introduction: Low carbohydrate (CH) diets have been used in the management of obesity-related T2DM, with modest results. "Classic" ketogenic diets (KD) used in epilepsy are very low CH (10-20 g/day), very high fat (87-90% of calories) diets. We report a pilot study of treatment of obesity-related T2DM with "classic" 3:1 [fat]:[carbohydrate + protein] weight ratio diet using the novel approach of a complete ready-made meal replacement program. Methods: In an open label study, T2DM patients with BMI ≥ 30 kg/m 2 were treated for 9 months with 3:1 KD (20 g CH/day, 1600 kcal/day), delivered as complete meal replacement (CMR). Weight, BMI, fasting plasma glucose (FPG), HbA1c, serum fasting insulin, lipid and leptin levels were evaluated monthly. Diabetic medications were adjusted as clinically indicated. Results: Eleven patients participated. Ten patients were treated for ≥ 4 days (modified intent to treat population, mITT); 5/10 stopped treatment early, 5/10 completed the study per protocol (PP subgroup, n = 5), and 6/10 (5/5 of PP subjects) achieved sustained T2DM remission. In the mITT population, mean BMI declined by 11.62% from baseline 39.84 kg/m 2 (p = 0.008), FPG by 21.56 mg/dL from 137.7 mg/dL (NS), HbA1cby 1.16% from 7.36% (p = 0.016) and insulin level by 14.22 from 23.18 µIU (NS). In the PP subgroup, mean BMI declined by 17.08% (p = 0.063), FPG by 47 mg/dl (p = 0.12), HbA1c by 1.36% (p = 0.063) and insulin by 14.76 µIU (NS). Triglyceride levels declined and HDL increased in the mITT population. KD was well tolerated. Adverse events, all transient and generally mild, caused no discontinuation, and included constipation (6/10), hunger (6) and diarrhea (2). Conclusion: Classic KD, delivered as CMR, may be effective in inducing remission in obesity-related T2D. Controlled studies are warranted.
